Use of Spontaneous Reporting Systems to Detect Host‐Medication Interactions: Sex Differences in Oral Anti‐Diabetic Drug‐Associated Myocardial Infarction

Background Medical treatment should be tailored to an individual's characteristics to optimize treatment benefits. We examined whether case-only analyses from spontaneous reporting systems can detect host-medication interactions in oral antidiabetic drug-associated myocardial infarction. Methods and Results Interaction between sex and use of oral antidiabetic drugs was mined among patients with myocardial infarction in the US Food and Drug Administration Adverse Event Reporting System from 2004 to 2014, including 55 718 males and 42 428 females. The odds ratio ( OR ) of multiplicative interactions was used to estimate sex-drug interaction. Detected signs of these interactions were then validated by a nested case-control study utilizing a healthcare record database, Taiwan's National Health Insurance Research Database, from 2001 to 2014, including 31 585 cases and 126 340 controls. In the US Food and Drug Administration Adverse Event Reporting System, a higher proportion of male than female patients used metformin (10.32% in males versus 7.82% in females) and sulfonylureas (4.75% in males versus 3.43% in females); after adjusting for patients' pharmacy-based chronic disease score, males had a higher risk of metformin-associated ( OR =1.07; 99% confidence interval, 1.00-1.14) and sulfonylureas-associated ( OR =1.21; 99% confidence interval, 1.10-1.33) myocardial infarction than females. Detected signs of sex-drug interactions were validated in the National Health Insurance Research Database ( OR for metformin=1.14; 99% confidence interval, 1.03-1.26; OR for sulfonylureas=1.13; 99% confidence interval, 1.02-1.25). Conclusions Males have a higher risk of metformin- and sulfonylureas-associated myocardial infarction than females, which suggests that sex-drug interactions are a key issue in diabetes mellitus treatment plan development. This case-only approach using information from spontaneous reporting systems may be a potential tool for screening host-medication interactions that cause adverse events.